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Title: DG DISPATCH - AHA: Reopro Effective And Safe In Antithrombotic Cocktail
URL: http://www.pslgroup.com/dg/143BEA.htm
Doctor's Guide
November 9, 1999


By Andrew Bowser
Special to DG News

ATLANTA, GA -- November 9, 1999 -- When a powerful anti-platelet drug is added to the standard anti-thrombotic cocktail, the dose of the fibrinolytic drug can be cut in half without any increase in bleeding complications, suggest the results of a large, randomized controlled trial.

In a press conference Monday (Nov. 8), Dr. Eugene Braunwald, of Brigham and Women's Hospital, in Boston, MA., reported on the Thrombin Inhibition in Myocardial Infarction 14 (TIMI 14) trial, a study that tested the hypothesis that abciximab (Reopro) could enhance thrombolysis in the setting of myocardial infarction marked by ST-segment elevation.

"We are very excited that this may be an important new direction," Dr. Braunwald said. "We all have realized increasingly that the platelet is playing a very important role not only in initiation of clot, but propagation of clot."

TIMI 14 extends the standard therapeutic cocktail of a thrombolytic agent, heparin and aspirin to include abciximab, an intravenous glycoprotein IIb/IIIa platelet inhibitor. Patients in the trial were all randomized to standard full dose thrombotherapy or half-dose thrombotherapy plus abciximab. Both t-PA (Activase) and r-PA (Retevase) were used as antithrombotic agents.

According to Dr. Braunwald, the combination of low-dose thromobolytic and full-dose platelet inhibitor resulted in a relative 50 percent to 55 percent increased rate of opening of the culprit artery (TIMI grade 3 flow at 60 minutes of 44 percent for full-dose thrombolytic, versus 73 percent for half-dose thrombolytic plus abciximab). Overall vessel patency approached 90 percent. The combinations were well-tolerated with no significant difference in major hemorrhage rate versus full-dose thrombotherapy, according to Dr. Braunwald.

But what will constitute an ideal combination cocktail therapy is still subject to debate and further research. Similar results are not available for TNK-tPA (tenecteplase), the newer, easier-to-administer genetic bioengineered thromolytic that in clinical trials has shown similar efficacy and safety to t-PA. "It really is a dead-ringer for t-PA in terms of the number of vessels it opens," Dr. Braunwald said.

There has also been increased interest in replacing heparin with newer low-molecular weight heparin, and trials will also be required to evaluate the role of the two other intravenous GP IIb/IIIa inhibitors in combination cocktails.

Related Link: ReoPro (abciximab).

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